Inflammation and benign and malignant tumors of the prostate afflict a large number of adult males. The etiology of these conditions is generally unknown, but may involve the normal aging process and associated alterations in hormonal balance. Mankind is not unique in this regard and other animals with a compact or solid prostate, such as dogs, suffer comparable disease states.
Chronic prostatitis is the most common chronic infection in adult males. It has been claimed to afflict about 35% of all male subjects at sometime during their lives. The typical patient is a middle-aged or elderly male referred for evaluation of repeated episodes of cystitis and pyelonephritis or epididymitis. Benign adenomatous hyperplasia of the prostate is also common malady seen in men over age 50 while adenocarcinoma of the prostate accounts for the majority of malignancies in men over age 65.
Chronic prostatitis can be classified into: (1) non-specific prostatitis, (2) specific prostatitis due in to infection with bacteria or fungi and (3) granulomatous, which may be non-specific (with unknown cause) or allergic, which is usually accompanied by some general allergic disease as bronchial asthma. Although granulomatous prostatitis is very rare, it should be differentiated from prostatic carcinoma.
The pathogenesis of the infectious types of prostatitis often is unclear. Possible routes of infection include: ascending urethral infection, reflux of infected urine into the prostatic ducts that empty into the prostatic urethra, invasion by rectal bacteria via direct extension or lymphogenous spread and hematogenous infection. The causative agents in chronic bacterial prostatitis are similar in type and prevalence to those responsible for urinary tract infection. Infection caused by common strains of Escherichia coli are predominant, although infections caused by species of Proteus, Klebsiella, Enterobacter, Pseudomonas and other less common types of gram-negative organisms are sometimes found. Mixed infections caused by two or more strains or classes of bacteria are not rare.
Opinions vary concerning the role of gram-positive bacteria as causative agents in chronic prostatitis. All agree that enterococcus is an important pathogen, whose persistence in the prostate causes relapsing urinary infections but whether other common gram-positive organisms such as micrococci, Staphylococci, Streptococci and diphtheroids are frequent or important prostatic pathogens is highly debatable.
Until the present time the treatment of chronic bacterial prostatitis has been mostly unsatisfactory. This is because the bacteria in prostatic fluid is a major cause of urinary infections in male patients who become symptomatic only when the bladder is infected. Most treatments involve maintaining the patient on a continuous low dosage of antimicrobial agent, which produces bactericidal bladder urine and prevents bacteria from infecting the bladder urine. This however does not kill the bacteria in the prostate who are protected from the action of the antimicrobial agent which cannot cross the prostatic epithelium in an effective concentration.
It is known that prostatic secretions of normal subjects contain much greater antibacterial activity than that found in men with proven bacterial prostatitis. This raises the possibility that a prostatic antibacterial factor might serve as a natural defense against prostatic and urinary infections. Purification and crystallization of prostatic antibacterial factor has revealed that its antibacterial activity is related to its concentration of zinc. Attempts to alter the level of zinc in the prostatic fluid by the oral administration of zinc preparations have failed.
As to the treatment of non-infectious prostatitis, benign adenomatous hyperplasia of the prostate and adenocarcinoma of the prostate, it is known that prostatic growth is under the control of androgen receptors in the prostate. The androgen receptors are stimulated by 5 a-dihydrotestosterone (DHT) which is produced in the prostate by enzymatic conversion of testosterone, which in turn is secreted by the testicular Leydig cells. While the pathogenesis of the above-mentioned conditions is generally unknown and as to latter two conditions, the definitive therapy is surgical, a treatment which inhibits the androgen receptors by blocking them or interfering with the enzymatic conversion of testosterone to DHT might have a beneficial effect by preventing reactivation of the disease or by providing long-term regression and, in the case of prostatic carcinoma, offer an alternative to surgery.
In view of the above, there is a need for an for an effective means of increasing the amount of prostatic antibacterial factor and for controlling the rate of prostatic growth by inhibiting the androgen receptors in the prostate. It is therefore an object of the present invention to provide a method of treatment for inflammatory conditions and benign and malignant tumors of the prostate by increasing the amount of prostatic antibacterial factor secreted by the prostate and by inhibiting the androgen receptors which control the rate of prostatic growth. Other objects and features of the invention will be in part apparent and in part pointed out hereinafter.
The invention accordingly comprises the methods hereinafter described and their equivalents, the scope of the invention being indicated in the following claims.